Chromosomal aberration induced by quinolone antibacterial agents

278 tion may be synergistic, zero or antagonistic depending on whether each interaction function is greater than, equal to, or less than zero. When V79 cells were treated with MMS and EMS for 3, 6 or 9 h, the combined effects of these two chemicals on survival and 6TG-resistant mutations were synergistic. 43 Kuroda, K., Y. Yamaguchi, G. Endo and Y.S. Yoo, Osaka City Institute of Public Health and Environmental Sciences, 543 Tojo-cho, Tennojiku, Osaka City 543, Japan Evaluation of river water by cytotoxicity, SCE and mutagenicity The pollution of the river Yodo is of much concern, because its water is used for drinking by 13 million people. Cytotoxicity, SCE and mutagenicity of the river (six sites), its six tributaries, and the river Neya into which sewage effluent and the river Yodo water flow were studied. The water was sampled every other month for over 1.5 years. The organic matter in the water was extracted with dichloromethane and was dissolved in dimethyl sulfoxide for the assays. Cytotoxicity was evaluated by mitotic index (MI) and second division index (DI) on the same chromosome preparation for SCE using V79 cells. Most of the extracts lowered the MI and the DI. The mean values of the MI and the DI for Kema (the lowest sampling site on the river Yodo) were lowest among the river Yodo sites. The river Hotani was most toxic of all the sampling sites. The mean values of SCE frequencies for Kema and the river Kizu were the highest, 1.3 times of the solvent control. Mutagenicity was assayed with TA100 and TA98. TA98 ( + $9 mix) was most sensitive and 87% of the extracts were mutagenic. Analysis by coefficients of correlation in mutagenicity revealed that pollutants in the river Neya were different from those of other rivers. Mutagenicity of the river Yodo in TA98 ( + $9 mix) had a high correlation with rainfall. 44 Long, C., K. Itoh, M. Takada and M. Mochizuki, Kyoritsu College of Pharmacy, Shibakoen 1-5-30, Minato-ku, Tokyo 105, Japan

Inhibitory effect of tea extracts and tea constituents on mutagenicity of a-hydroperoxide of N-nitroso-N-methylbenzylamine Tea extracts and tea constituents have been reported to protect rats against esophageal cancer induced by N-nitroso-N-methylbenzylamine, a possible human esophageal carcinogen. In the present study, the effects of extracts from three kinds of tea (green tea, oolong tea and jasmine tea), and their main constituents, (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG), on mutagenicity of N-nitroso-N-(hydroperoxymethyl)benzylamine (NHPMBz) were examined in Salmonella typhimurium TAI00 and E. coli WP2 hcr-. NHPMBz is a direct-acting mutagen in bacterial test system without $9 mix. EGC and EGCG were isolated from the green tea extract by Sephadex LH-20 column chromatography. The mutagenicity of NHPMBz was significantly inhibited by the tea extracts, EGC and EGCG, and the degree of inhibition depended on the dose. To elucidate the mechanism of inhibition, NHPMBz was treated with the green tea extract, EGC or EGCG in phosphate buffer. Decomposition of the mutagen was observed by HPLC. This indicated that tea constituents decomposed the mutagen, NHPMBz. 45 Maekawa, T., M. Irie, Y. Inoue and M. Taguchi, Kanebo Pharmaceuticals Research Center, 5-90, Tomobuchi-cho 1-chome, Miyakojima-ku, Osaka 534, Japan Chromosomal aberration induced by quinolone antibacterial agents It has been reported that some quinolone antibacterial agents (quinolones) induced positive mutagenic responses in vitro (gene mutation in mouse lymphoma L5178Y cells, UDS in rat primary hepatocytes). In the present study, clastogenic effects of various quinolones, such as enoxacin (ENX), ciprofloxacin (CPFX), lomefloxacin (LFLX), norfloxacin (NFLX), and ofloxacin (OFLX), were investigated following in vitro and in vivo treatment. To evaluate in vitro clastogenic effects,

279 chromosomal aberration tests were performed on Chinese hamster lung (CHL) cells at 100-500 /xg/ml for 24 h exposure. CPFX and LFLX showed a significant increase in frequency of chromosomal aberration at more than 300/zg/ml causing approximately 70% reduction in mitotic index, while ENX, NFLX, and OFLX did not show that. The aberrations observed were primarily chromatid breaks and chromatid exchanges. To evaluate in vivo clastogenic effects, mouse bone marrow micronucleus tests were performed after single-dose administration with 24-h sampiing time. No quinolone tested induced a positive reaction up to 3000 mg/kg p.o. It is generally considered that quinolones inhibit bacterial DNA gyrase (Gy), and also mammalian topoisomerase II (topo II) at higher concentration. Inhibitory activities of quinolones were determined on Gy from E. coli and topo II from CHL cells by DNA supercoiling assay and DNA relaxing assay, respectively. All quinolones tested were very much more effective on Gy than on topo II. ENX was more effective on topo II than CPFX or LFLX which induced chromosomal aberration. In conclusion, some quinolones (CPFX and LFLX) showed in vitro clastogenic responses in relation to cytotoxicity, but it is not clear whether inhibition of topo II directly causes clastogenicity. 46 Manabe, Y., M. Asakura and F. Jitsunari, Kagawa Medical School, 1750-1 Miki-cho, Kita-gun, Kagawa 760, Japan Extrapolation from concentration of air pollutants to concentration of mutagens and mutagenicity of airborne particles using multiple regression analysis To estimate the long-term health effects on human exposed to mutagens/carcinogens in airborne particles, the methodology to determine the exposure level of humans is necessary. The mutagenicity assay (Ames assay) is very useful, but it needs complicated operations. On the other hand, a local self-governing body is in duty bound to report the concentration of air pollutants every year by the Air Pollution Control Act in Japan.

Therefore, this study aimed to extrapolate from concentration of air pollutants to concentration of benzo[a]pyrene (B(a)P), benzo[ghi]perylene (B(ghi)P) and mutagenic activity of airborne particles using multiple regression analysis. For explanatory variables, data on 79 items in total collected with 10 air pollutants (e.g., CO, NO, CH 4) at each of 11 stations during April 1986 to March 1989 were used. For response variables, concentrations of B(a)P, B(ghi)P and mutagenicity during the same period were used. In the case of B(a)P, 25 items were selected out by regression analysis. The coefficient of determination adjusted for the degrees of freedom (RR') and the multiple correlation coefficient adjusted for degrees of freedom (R') were 0.9247 and 0.9616, respectively. In the case of B(ghi)P and mutagenicity with S. typhimurium strains TA98 and TA100 in the presence/absence of $9 mix, RR' and R' also showed high values. In order to predict the concentration of B(a)P, B(ghi)P and mutagenicity precisely, this study should be developed more completely. 47 Mano, H., M. Akashi a and H. Hayatsu a, Department of Hygiene and Preventive Medicine, Niigata University School of Medicine, Asahimachi-dori, Niigata 951 and a Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700, Japan Mutagenicity of blue rayon extract of human bile in the Ames test using Salmonella typhimurium TA98 In order to clear the etiological role of human bile in biliary tract cancer, we analyzed its mutagenicity. The mutagenicity of whole human bile was examined in the Ames Salmonella/microsome assay. Human bile samples were obtained from gallbladders resected for cholelithiasis, choledocholithiasis, gallbladder cancer, extrahepatic bile duct cancer and other various diseases. For extraction and purification of mutagenic compounds, the collected bile was treated with blue rayon, and its extract was then assayed in the Ames test using Salmonella typhimurium